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Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence.

Nat Commun. 2019-05; 
SliepenKwinten,HanByung Woo,BontjerIlja,MooijPetra,GarcesFernando,BehrensAnna-Janina,RantalainenKimmo,KumarSonu,SarkarAnita,BrouwerPhilip J M,HuaYuanzi,TolazziMonica,SchermerEdith,TorresJonathan L,OzorowskiGabriel,van der WoudePatricia,de la PeñaAlba Torrents,van BreemenMariëlle J,Camacho-SánchezJuan Miguel,BurgerJudith A,Medina-RamírezMax,GonzálezNuria,AlcamiJose,LaBrancheCelia,ScarlattiGabriella,van GilsMarit J,CrispinMax,MontefioriDavid C,WardAndrew B,KoopmanGerrit,MooreJohn P,ShattockRobin J,BogersWilly M,WilsonIan A,SandersRogi
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Peptide Synthesis To test peptide binding to patient MSK-HN1 HLAs that are not HLA-A*02:01, T2 cells were individually electroporated with 2 µg pcDNA3.1–HLA–P2A–eGFP constructs (HLA sequences synthesized by GenScript) Get A Quote

摘要

Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significant... More

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